Neurosurgery Department, School of Medicine, Celal Bayar University, Manisa, Turkey.
Neurosurgery Department, School of Medicine, Koc University, Istanbul, Turkey.
Anticancer Agents Med Chem. 2019;19(9):1120-1131. doi: 10.2174/1871520619666190405112507.
Punicic Acid (PA) is a polyunsaturated fatty acid that accounts for approximately 70%- 80% of Pomegranate Seed Oil (PSO). PA possesses strong antioxidant, anti-inflammatory, anti-atherogenic effects, and anti-tumorigenic properties. Pomegranate extracts have been shown to have anticancer activity in many studies. However, there is no evidence for the effect of PSO on T98 glioblastoma cells. Therefore, the present study was the first to investigate the mechanisms induced by PA on T98 cells, which is one of the major compounds extracted from PSO.
The effects of PA on cell viability; oxidative stress; and migration, proliferation, and apoptosis at the IC50 dose were studied.
The proliferation and migration were inhibited in the treated group compared to the non-treated group by 9.85µl/ml PA. The difference was statistically significant (***p<0.001). Furthermore, PA-induced apoptosis in the T98 glioblastoma cells compared to non-treated group and the difference was statistically significant (***p<0.001). Apoptosis was determined via immunocytochemistry staining of caspase-3, caspase-9 and TUNEL methods. Apoptosis was checked by flow cytometry (using caspase 3 methods) and Scanning Electron Microscopy Analysis. We also investigated the potential signaling pathway underlying this apoptotic effect. The immunocytochemical stainings of PI3K/ Akt-1/ mTOR-1 demonstrated that Akt-1 staining was increased with PA treatment similar to mTOR-1 and PI3K staining (***p<0.001). These increases were statistically significant compared to the non-treated group.
PA exhibited exceptional abilities as an anticancer agent against GBM cells. The use of punicic acid in combination with other drugs used in the treatment of glioblastoma may increase the efficacy of the treatment. This study provided a basis for future investigation of its use in preclinical and clinical studies.
共轭亚油酸（PA）是一种多不饱和脂肪酸，约占石榴籽油（PSO）的 70%-80%。PA 具有很强的抗氧化、抗炎、抗动脉粥样硬化和抗肿瘤作用。许多研究表明，石榴提取物具有抗癌活性。然而，没有证据表明 PSO 对 T98 胶质母细胞瘤细胞有影响。因此，本研究首次研究了 PA 对 T98 细胞的作用机制，T98 细胞是从 PSO 中提取的主要化合物之一。
研究了 PA 对细胞活力、氧化应激以及在 IC50 剂量下增殖、迁移和凋亡的影响。
与未处理组相比，9.85µl/ml 的 PA 处理组的增殖和迁移受到抑制，差异具有统计学意义（***p<0.001）。此外，与未处理组相比，PA 诱导 T98 胶质母细胞瘤细胞凋亡，差异具有统计学意义（***p<0.001）。通过 caspase-3、caspase-9 和 TUNEL 免疫细胞化学染色法检测凋亡。通过流式细胞术（使用 caspase 3 法）和扫描电子显微镜分析检查凋亡。我们还研究了潜在的信号通路。PI3K/Akt-1/mTOR-1 的免疫细胞化学染色显示，PA 处理后 Akt-1 染色增加，与 mTOR-1 和 PI3K 染色相似（***p<0.001）。与未处理组相比，这些增加具有统计学意义。
PA 对 GBM 细胞表现出卓越的抗癌能力。将共轭亚油酸与用于治疗胶质母细胞瘤的其他药物联合使用，可能会提高治疗效果。本研究为今后在临床前和临床研究中使用它提供了依据。
